By
Joyce Peterson

Mice that receive sporadic, high-level doses of antibiotics—emulating typical prescriptions for children—experience significant changes in body composition and microbiome, according to research published June 30 in Nature Communications.

The results of the research, led by Martin Blaser, M.D., director of the NYU Human Microbiome Program at NYU School of Medicine, are consistent with those seen in human epidemiologic studies, says George Weinstock, Ph.D., director for microbial genetics at The Jackson Laboratory and, with JAX colleagues Erica Sodergren, Ph.D., and Yanjiao Zhou, Ph.D., a coauthor of the paper.

“Further study is needed to define how these results apply to children,” Weinstock says. “But these findings do suggest it would be valuable to revisit criteria and guidelines for administering antibiotics to patients, especially children.”

Antibiotics are routinely administered to livestock to promote growth, but in low levels and consistent doses. The researchers tested two antibiotics commonly prescribed in children—tylosin and amoxicillin—in a typical high-dose, short course regime, and found that each had different effects on both phenotypes and microbiome composition. Both yielded growth acceleration and increased lean mass, but amoxicillin promoted higher bone density and tylosin was associated with increased fat. The fat mass gains were lower and didn’t last as long as those observed after agricultural-style antibiotic dosing.

Both antibiotics decreased microbiota diversity, with tylosin dosing having the quicker, longer-lasting and larger effect, and it particularly reduced bacteria in the phylum Bacteroidetes. In mice receiving amoxicillin, the researchers observed a shift only after all three doses, and the microbiome community reverted quickly (within one week) to a composition similar to that of the control mice.

Tylosin increased micro- and overall steatosis (infiltration of fat into the liver tissue, indicating a metabolic perturbation), while amoxicillin reduced microsteatosis. Tylosin also increased expression of genes related to metabolic function (lipid metabolism, cellular movement, etc.) long after the final course, suggesting that early-life antibiotic exposures can have long-lasting metabolic influences.